Jérémie J P Lebrec

Learn More
Despite the current trend towards large epidemiological studies of unrelated individuals, linkage studies in families are still thoroughly being utilized as tools for disease gene mapping. The use of the single-nucleotide-polymorphisms (SNP) array technology in genotyping of family data has the potential to provide more informative linkage data.(More)
We describe an empirical Bayesian linear model for integration of functional gene annotation data with genome-wide association data. Using case-control study data from the North American Rheumatoid Arthritis Consortium and gene annotation data from the Gene Ontology, we illustrate how the method can be used to prioritize candidate genes for further(More)
We present a unified approach to selection and linkage analysis of selected samples, for both quantitative and dichotomous complex traits. It is based on the score test for the variance attributable to the trait locus and applies to general pedigrees. The method is equivalent to regressing excess IBD sharing on a function of the traits. It is shown that(More)
In this study, we attempted to confirm genetic linkage to developmental dyslexia and reading-related quantitative traits of loci that have been shown to be associated with dyslexia in previous studies. In our sample of 108 Dutch nuclear families, the categorical trait showed strongest linkage to 1p36 (NPL-LOD = 2.1). LOD scores for quantitative traits(More)
In Genomewide association (GWA) studies investigating thousands of SNPs, large sample sizes are needed to obtain a reasonable power after correction for multiple testing. To obtain the necessary sample sizes, data from different populations/cohorts are combined. The problem of pooling evidence across cohorts bears some resemblance with meta-analysis of(More)
The mean identity-by-descent (IBD) specification used in the Generalized Estimating Equations (GEE) methodology for linkage is only valid, strictly speaking, under the assumption of fully polymorphic markers. In practice, markers often provide only partial IBD information, which can potentially result in inconsistency of the locus location and gene effect(More)
For linkage analysis in affected sibling pairs, we propose a regression model to incorporate information from a disease-associated single-nucleotide polymorphism located under the linkage peak. This model can be used to study if the associated single-nucleotide polymorphism marker partly explains the original linkage peak. Two sources of information are(More)
The transmission/disequilibrium test statistic has been used for assessing genetic association in affected-parent trios. In the presence of multiple tightly linked marker loci where local dependency may exist, haplotypes are reconstructed statistically to estimate the joint effects of these markers. In this manuscript, we propose an alternative to the(More)
We derive a test for linkage in a Generalized Linear Mixed Model (GLMM) framework which provides a natural adjustment for marginal covariate effects. The method boils down to the score test of a quasi-likelihood derived from the GLMM, it is computationally inexpensive and can be applied to arbitrary pedigrees. In particular, for binary traits, relative(More)
In order to study family-based association in the presence of linkage, we extend a generalized linear mixed model proposed for genetic linkage analysis (Lebrec and van Houwelingen (2007), Human Heredity 64, 5-15) by adding a genotypic effect to the mean. The corresponding score test is a weighted family-based association tests statistic, where the weight(More)